DESCRIPTION: (Verbatim from applicant?s abstract) This competing continuation application represents a logical continuation of the plan based on the results of the present RO1. NS34949 was submitted in 1995 and renewed in 1998. The PI changed institutions in January 2000. The new project expands the scope of the current ROl by emphasizing a longitudinal population-based component to brain arteriovenous malformation (BAVM) basic epidemiology and natural history. In Specific Aim I we will re-examine the natural history of BAVM using a hybrid referral and population-based approach. enabling us to resolve the contradictory hypotheses on whether initial presentation determines future natural history. More importantly, we will more accurately estimate rates of subsequent hemorrhage from which to construct clinical trials. In Specific Aim II we will determine the influence of genetic factors known to influence the incidence and outcome from other intracranial hemorrhage (ICH) syndromes (Apolipoprotein Epsilon 2 and Epsilon 4 alleles: APOE2 and 4). In Specific Aim III we use a population-based registry (KPNC) to clarify the ascertainment and distribution of BAVM cases by race-ethnic group. The methods consist using our well-established case ascertainment and database registry of BAVM cases in the San Francisco Bay Area. New case material derives from the referral population at UCSF and, after correcting for overlap, a population-based approach in conjunction with Kaiser Permanente Northern California (KPNC: about 3 million covered lives). The general hypotheses are that there are at least two biologic clinical behaviors of BAVMs. We propose to identify risk factors for spontaneous BAVM hemorrhage and treatment outcome. Although the primary reason to treat BAVMs is prophylaxis against intracranial hemorrhage (ICH) treatment decisions must account for both treatment and natural history risk. However, data on these two distinct risks are currently insufficient, which greatly hamper the formulation of randomized clinical trials of BAVM treatment comparing different treatment modalities. The significance of this work is that by clearly documenting natural history risks, a risk-based strategy for treatment will serve as the basis for one or more multicenter (possibly multinational) clinical trials. Such trials may include some combination of surgical, endovascular, radiosurgical or medical treatment and can specifically weigh treatment against natural history risk. The accomplishment of these aims could bring to treating physicians and surgeons the means to further decrease morbidity from BAVMs and a basis for more rational and cost-effective decision-making as regards interventional therapy.